Macrophage migration inhibitory factor: Association of -794 CATT5-8 and -173 G>C polymorphisms with TNF-? in systemic lupus erythematosus

Several studies have found that obesity and increased adiposity mainly in the abdominal region, are associated with low-grade inflammation, insulin resistance (IR), impaired glucose homeostasis and comorbidities such as type 2 diabetes mellitus (T2D) and cardiovascular disease. The macrophage migration inhibitory factor (MIF), is a proinflammatory cytokine involved in autoimmune and inflammatory diseases. However, currently it is suggested that MIF is involved in the inflammatory process associated with obesity and the metabolic control of the complications associated with obesity. Different studies show consistently, increased serum levels of MIF in subjects with obesity, type 2 diabetes and diabetics with microvascular complications (nephropathy, retinopathy and diabetic foot syndrome). The relationship of the MIF to the regulation of glucose metabolism and apoptosis of pancreatic _ cells, and the association of some functional polymorphisms in the promoter of the MIF gene with obesity and diabetes.This review summarizes, the knowledge based on clinical and epidemiological studies on the role of MIF in obesity and type 2 diabetes. " 2014, Investigacion Clinica (Venezuela). All rights reserved.",,,,,,,,,"http://hdl.handle.net/20.500.12104/42634","http://www.scopus.com/inward/record.url?eid=2-s2.0-84908503529&partnerID=40&md5=0cd8edd1cbe7f42ec20a0a221c8eaa7

Regulation of the organic pollution level in anaerobic digesters by using off-line COD measurements

Background: Several association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.Methods: This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ? 100 mg/dL, triglycerides ? 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ? 95 thpercentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ? 95 thpercentile and insulin resistance HOMA-IR ? 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP.Results: For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01). The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02) in comparison with C/C genotype.Conclusions: The -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the increase of total cholesterol levels in Mexican children. " 2012 De la Cruz-Mosso et al; licensee BioMed Central Ltd.",,,,,,"10.1186/1471-2431-12-41",,,"http://hdl.handle.net/20.500.12104/44169","http://www.scopus.com/inward/record.url?eid=2-s2.0-84858966556&partnerID=40&md5=aaa17193e779c0fa53b5fcc85c4eb66a",,,,,,,,"BMC Pediatrics",,,,"12",,"Scopu

Portfolio optimisation under flexible dynamic dependence modelling

The macrophage migration inhibitory factor (MIF) is related to the progression of atherosclerosis, which, in turn, is a key factor in the development of acute coronary syndrome (ACS). MIF has a CATT short tandem repeat (STR) at position -794 that might be involved in its expression rate. The aim of this study was to investigate the association between the -794 CATT5-8 MIF gene polymorphism and susceptibility to ACS in a western Mexican population. This research included 200 ACS patients classified according to the criteria of the American College of Cardiology (ACC) and 200 healthy subjects (HS). The -794 CATT5-8 MIF gene polymorphism was analyzed using a conventional polymerase chain reaction (PCR) technique. The 6 allele was the most frequent in both groups (ACS: 54% and HS: 57%). The most common genotypes in ACS patients and HS were 6/7 and 6/6, respectively, and a significant association was found between the 6/7 genotype and susceptibility to ACS (68% versus 47% in ACS and HS, resp., P=0.03). We conclude that the 6/7 genotype of the MIF -794 CATT5-8 polymorphism is associated with susceptibility to ACS in a western Mexican population. © 2014 Emmanuel Valdés-Alvarado,et al

MIF and TNF? serum levels in rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs: A cross-sectional study

Macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF?) play a pivotal role in rheumatoid arthritis (RA). MIF is considered a relevant cytokine because it appears before TNF? in the inflammatory cascade thus stimulating TNF? production and MIF's relationship with traditional synthetic disease modifying antirheumatic drugs (sDMARDs) is unknown. In this cross-sectional study, we investigated the association of MIF and TNF? serum levels with methotrexate (MTX) and in combination with chloroquine (CLQ) and sulfasalazine (SSZ) in RA patients classified according to the ACR/EULAR 2010 criteria. Patients were divided into three groups: MTX-monotherapy group (n40), MTX combination therapy groups: MTXCLQ (n41), and MTXCLQSSZ (n42). MIF and TNF? serum levels were determined by ELISA. We found high levels of ESR, CRP, RF, and anti-CCP in all therapy groups. Furthermore, we subclassified 97 patients with established RA (?2 years of disease duration) and found that TNF? serum levels were lower in the combination therapy group (MTX + CLQ + SSZ) in comparison with the monotherapy MTX group (16.7pg/mL versus 13.6pg/mL, p0.02). However, we did not find differences between sDMARD therapies in MIF serum levels. We did find a significant reduction in MIF serum levels in patients treated with oral steroids compared with patients without oral steroids (1.7ng/mL versus 4.3ng/mL, p<0.001). In conclusion, this study supports the role of sDMARDs in modifying TNF? serum levels and oral steroids MIF serum levels. Nevertheless, we found that MIF serum levels are not modified by sDMARD treatment. � 2015 Informa Healthcare USA, Inc. All rights reserved

Macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794 CATT5-8 and-173 G&gt;C): Association with MIF and TNFα in psoriatic arthritis

Psoriatic arthritis (PsA) is an autoimmune disease with a complex interaction of gene and with a dysregulation of pro-inflammatory cytokine such as Macrophage migration Inhibitory Factor (MIF) and Tumor Necrosis Factor-alpha (TNFα). Two polymorphisms identified in the promoter region of the MIF gene have been described: the STR-794 CATT5-8 (rs5844572) and the SNP-173 G>C (rs755622), which are associated with increased MIF levels in circulation and with autoimmune diseases in several populations. In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with PsA susceptibility and clinical variables as well as with MIF and TNFα serum levels in a Mexican-Mestizo population. Genotyping of the-794 CATT5-8 and-173 G>C MIF polymorphisms was performed by PCR and PCR-RFLP respectively in 50 PsA patients and 100 healthy subjects (HS). MIF and TNFα serum levels were determined by ELISA. A significant increase of MIF (PsA: 7.8 vs. HS: 5.25 ng/mL; p C MIF were associated with susceptibility to PsA. In conclusion the-173*C allele is associated with susceptibility to PsA in Mexican-Mestizo population, whereas the correlation between MIF and TNFα soluble levels provided evidence that both cytokines are closely related in the pathophysiology of the PsA. © 2014, International Journal of Clinical and Experimental Medicine. All rights reserved

Macrophage migration inhibitory factor: Association of -794 CATT5-8 and -173 G&gt;C polymorphisms with TNF-α in systemic lupus erythematosus

Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory cytokine associated with the pathogenesis of autoimmune inflammatory diseases. There is evidence that MIF functions in a positive feedback loop with TNF-α that could perpetuate the inflammatory process in systemic lupus erythematosus (SLE). In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with SLE as well as with MIF and TNF-α serum levels in a Mexican-Mestizo population. Genotyping of the -794 CATT5-8 (rs5844572) and -173 G&gt;C (rs755622) MIF polymorphisms was performed by PCR and PCR-RFLP, respectively in 186 SLE patients and 200 healthy subjects. MIF and TNF-α serum levels were determined by ELISA. A significant increase of MIF and TNF-α levels was found in SLE patients. According to a genetic model, we found a significant association of genotypes carrying the -794 CATT7 and -173*C risk alleles with susceptibility to SLE and with a significant increase of TNF-α. In conclusion, MIF gene polymorphisms are associated with SLE susceptibility and with an increase of TNF-α serum levels in a Mexican-Mestizo population. © 2014 American Society for Histocompatibility and Immunogenetics

Isolated vein thrombosis of the posterior fossa presenting as localized cerebellar venous infarctions or hemorrhages

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction- restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/ 5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI- 1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients. " Springer-Verlag 2011.",,,,,,"10.1007/s00296-011-2279-y",,,"http://hdl.handle.net/20.500.12104/43463","http://www.scopus.com/inward/record.url?eid=2-s2.0-84872262801&partnerID=40&md5=dc103ddfb9116944c55d3987e9a0a05

Macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794 CATT5-8 and-173 G&gt;C): Association with MIF and TNF? in psoriatic arthritis

Psoriatic arthritis (PsA) is an autoimmune disease with a complex interaction of gene and with a dysregulation of pro-inflammatory cytokine such as Macrophage migration Inhibitory Factor (MIF) and Tumor Necrosis Factor-alpha (TNF?). Two polymorphisms identified in the promoter region of the MIF gene have been described: the STR-794 CATT5-8 (rs5844572) and the SNP-173 G>C (rs755622), which are associated with increased MIF levels in circulation and with autoimmune diseases in several populations. In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with PsA susceptibility and clinical variables as well as with MIF and TNF? serum levels in a Mexican-Mestizo population. Genotyping of the-794 CATT5-8 and-173 G>C MIF polymorphisms was performed by PCR and PCR-RFLP respectively in 50 PsA patients and 100 healthy subjects (HS). MIF and TNF? serum levels were determined by ELISA. A significant increase of MIF (PsA: 7.8 vs. HS: 5.25 ng/mL; p C MIF were associated with susceptibility to PsA. In conclusion the-173*C allele is associated with susceptibility to PsA in Mexican-Mestizo population, whereas the correlation between MIF and TNF? soluble levels provided evidence that both cytokines are closely related in the pathophysiology of the PsA. � 2014, International Journal of Clinical and Experimental Medicine. All rights reserved

PAI-1 mRNA expression and plasma level in rheumatoid arthritis: Relationship with 4G/5G PAI-1 polymorphism

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction- restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/ 5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI- 1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients. © Springer-Verlag 2011

The −675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the −675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the −675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The −675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81–3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62–4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31–2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84–3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the −675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE